The purpose of this study is to demonstrate that chromosomal alternations are mechanistically related to origin and/or progression of chemically induced mouse skin tumors. Using techniques recently developed in our laboratory we will study chromosomal anomalies in benign and maligant tumors induced in mice by two-stage carcinogenesis, using DMBA as the initiator and TPA as the promoter. Chromosome findings in these tumors will be correlated with the histopathological characterization of the tumor and with markers of tumor progression. Other sets of experiments will be aimed to investigate the specificity of the chromosomal anomalies. For this purpose the chromosomes of squamous cell carcinomas induced by three different carcinogens and three different protocols will be studied and the non-random chromosome alterations obtained in the different experiments will be compared. The influence of the genetic background of the mice on the number and type of chromosome alterations will also be studied in tumors induced in different strains or stocks of mice. Once we have defined the characteristic and specificity of the chromosomal alterations in skin tumors we will focus our study on the mechanisms of action of chromosome anomalies at the molecular level. Gene rearrangement and gene expression will be studied using specific DNA probes for oncogenes that have been mapped in the affected chromosomes.